In the year 2000, an estimated 22 million people were suffering from cancer worldwide and 6.2 millions deaths were attributed to this class of diseases. Every year, there are over 10 million new cases and this estimate is expected to grow by 50% over the next 15 years (WHO, World Cancer Report. Bernard W. Stewart and Paul Kleihues, eds. IARC Press, Lyon, 2003). Current cancer treatments are dominated by invasive surgery, radiation therapy and chemotherapy approaches, which are frequently ineffective and can have potentially severe side-effects, non-specific toxicity and/or cause traumatizing changes to ones body image and/or quality of life. One of the causes for the inadequacy of current cancer treatments is their lack of selectivity for affected tissues and cells. Treatment with greater selectivity for cancer cells would leave normal cells unharmed thus improving outcome, side-effect profile and quality of life.
The selectivity of cancer treatment can be improved by targeting molecules that are specific to cancer cells and not found on normal cells. These molecules can then be used as a target to antibody-based diagnostic or therapeutics or for drugs capable of altering their function.
HnRNPG or heterogeneous ribonucleoprotein G is also known as RBMX. It is primarily localized in the nucleus where it has been found to form complexes with several proteins, to regulate the splicing of some genes, and to influence the DNA repair functions of p53 (Li et al 2003, Venables et al 2000; Najib et al 2005). Many of these mechanisms have been linked to tumor formation (U.S. Pat. No. 6,627,405 B1; Nandabalan et al 2003). Recently, Shin et al 2006 and 2007 have reported that normal HnRNPG has tumor suppressor functions, that expression has been found to be diminished in tumor cells and have established a link between p53 regulated DNA repair functions and normal HnRNPG expression. Shin et al 2006 describes a tumor associated form of HnRNPG with a single amino acid change at residue 22 in the RNA binding domain and reports detection by immunohistochemistry of membrane associated expression of HnRNPG.
PSCA is a 123 amino-acid glycosyl-phosphotidyl-inositol (GPI)-linked glycoprotein found on the cell surface. Its mRNA is expressed in normal tissues but up-regulated in neoplastic tissues (Gu et al., Cancer Res., 2005, 65:9495). Its overexpression has been linked to prostate cancer (Zhigang and Wenlv, World J. Surg. Oncol., 2004a, 2:13, Zhigang and Wenlv, Jpn. J. Clin. Oncol., 2004b, 34:414), pancreatic cancer (Wente et al., Pancreas, 2005, 31:119) and bladder cancer (Amara et al., Cancer Res., 2001, 61:4660). Anti-PSCA monoclonal antibodies, humanized or obtained from transgenic mouse (Xenomouse) have been developed (U.S. Pat. No. 6,825,226, US 2006/0269557, WO 2005/118864) and some are being evaluated for the treatment of cancer.